How to Diagnose and Manage Acute and Recurrent Gout: ACP Guideline

By Megan Brooks

NEW YORK (Reuters Health) - Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and colchicine are appropriate to treat patients with acute gout, the American College of Physicians (ACP) recommends in an evidence-based clinical practice guideline published today.

"Physicians should consider using corticosteroids first in patients without contraindications because they are one of the most effective anti-inflammatory medications available and they are as effective as NSAIDs for managing acute gout but have fewer adverse effects," ACP President Dr. Nitin S. Damle, said in a statement.

"Although a generic formulation of colchicine is now available, it is more expensive than NSAIDs or corticosteroids. This is an important consideration for patients, especially as prescription drug prices continue to increase," Dr. Damle added.

If colchicine is used to treat acute gout, the guideline recommends a low dose (1.2 mg followed by 0.6 mg one hour later). The evidence shows that lower doses are as effective as higher doses (1.2 mg followed by 0.6 mg/h for six hours) at reducing pain and are associated with fewer gastrointestinal adverse effects, it says.

As for diet, there currently is not enough evidence to recommend gout-specific dietary advice or therapies (such as reduced intake of red meat, fructose, and alcohol) to ease symptoms, the guideline says. One systematic review and one randomized controlled trial found that dietary changes reduced urate levels, but no study examined the effect of any dietary intervention on clinical outcomes, such as acute gout flares, note Dr. Amir Qaseem and the ACP Clinical Guidelines Committee.

The guideline recommends against initiating long-term uric acid-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.

"Gout symptoms are mostly caused by an inflammatory reaction to the deposition of uric acid crystals in the joint. This is a result of increased uric acid levels above a saturation point in blood," Dr. Damle told Reuters Health by email.

"While the evidence supports the benefits of using uric acid-lowering therapy for shorter duration to reduce gout flares, the benefits of long-term usage for 12 or more months in patients with a single or infrequent gout attacks have not been studied. In most patients, it is not clearly necessary to start uric acid-lowering therapy in cases where the individuals would have no or infrequent recurrences," Dr. Damle said.

In cases of recurrent gout (two or more episodes per year) or problematic gout (for example, gout associated with tophi, chronic renal disease, or urolithiasis), the guideline recommends shared decision making with the patient to review possible benefits, harms, costs and individual preferences, including concomitant prophylaxis, before initiating uric acid-lowering therapy.

"High-quality evidence showed that prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy. Moderate-quality evidence also showed that continuing prophylactic treatment for more than 8 weeks was more effective than shorter durations to help prevent gout flares in patients initiating urate-lowering therapy," the guideline states.

"Target thresholds for serum urate levels rely on the chemistry of uric acid, which is soluble up to a concentration of about 404 mcmol/L (6.8 mg/dL), above which precipitation may occur. However, this threshold is not absolute because patients with higher serum urate levels may still be asymptomatic, and some may have acute flares below this threshold. Although there is an association between lower urate levels and fewer gout flares, the extent to which use of urate-lowering therapy to achieve various targets can reduce gout flares is uncertain," the guideline says.

It also notes that there is insufficient evidence for monitoring serum urate levels in patients with gout.

Dr. Damle told Reuters Health, "One ACP Clinical Guidelines Committee recommendation is to perform comparative effectiveness studies to evaluate the benefits and harms of 'treat to target' over 'treat to avoid symptoms.'"

The co-authors of a linked editorial have a different view on monitoring urate levels and treat-to-target.

The guideline acknowledges that urate-lowering therapy (ULT) reduces serum urate levels (a strong predictor of flares), and there is data to support an association between lower serum urate levels and lower risk for flares, Dr. Tuhina Neogi from Boston University and Dr. Ted Mikuls from the University of Nebraska in Omaha explain.

"It is therefore puzzling," they write, "that the strength of evidence for monitoring of serum urate levels, a prerequisite to ensuring adequate ULT dosing, was judged to be low. Using extrapolation similar to that applied to the assessment of gout flare management, we found at least moderate strength of evidence supporting monitoring of serum urate levels."

On the issue of treating to target, Drs. Neogi and Mikuls note that the guideline suggests that a "reactive 'treat-to-avoid-symptoms' approach may be a reasonable strategy with ULT instead of a proactive 'treat-to-target' strategy because the latter has not been adequately tested. However, the treat-to-avoid-symptoms approach has not been tested either."

"We acknowledge," they add, "that the existing literature only indirectly addresses what the optimal serum urate target is. However, it is a disservice to our patients and primary care colleagues to suggest that treating to avoid symptoms is acceptable with ULT in the absence of evidence. At the very least, based on the biochemistry of urate, a treatment target below the physiologic threshold of urate crystallization (<6.8 mg/dL) would be appropriate, even if a lower target is not yet supported by randomized trials."

Drs. Neogi and Mikuls say a target of <6.8 mg/dL (or <357 mcmol/L, <6 mg/dL with assay variation taken into account) "seems reasonable, based on the authors' own admission that serum urate levels exceeding this threshold are the cause of gout. As an example, no one would advocate for a treat-to-avoid-symptoms strategy for diabetes."

In a second editorial, Dr. Robert McLean of Northeast Medical Group, New Haven, Connecticut, says the ACP recommendations "likely will ignite controversy" because they have "some distinct differences" from the 2012 American College of Rheumatology (ACR) guidelines.

As the ACP guideline committee evaluated the latest evidence, Dr. McLean explains, it became clear that some aspects of gout management that have evolved in recent years and were included in the 2012 ACR guideline - particularly the treat-to-target strategy to lower serum uric acid below 6.0 mg/dL - were based on retrospective studies or studies that used surrogate outcomes (uric acid levels) rather than clinical ones (frequency of gout episodes).

"A recent commentary in a rheumatology journal acknowledges that the ACR's treat-to-target recommendation is based on indirect evidence and no randomized trials. With the limitations of this evidence, the ACP committee thought it inappropriate to make the treat-to-target recommendation that the ACR made," Dr. McLean points out.

Summing up, he says, "Clinicians must always do what is appropriate and best for the patient at that time. Even if a guideline recommendation is based on high-quality evidence, following the path it specifies might not be right for a particular patient. When we deviate from a clinical practice guideline recommendation, we should engage the patient in this decision and document in our clinical records why care deviated from the guidelines. Guidelines are not meant to be absolute directives; thus, it becomes problematic when third-party payers or regulatory agencies treat them as such."

The companion ACP guideline on diagnosing gout advises synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible gout.

"While joint aspiration with synovial fluid analysis for uric acid crystal analysis is the reference standard for diagnosing gout, most patients are seen initially by their primary care physician or an emergency room physician where synovial fluid analysis is less frequently and less easily performed," Dr. Damle said in a statement. "In certain situations, physicians should use clinical judgment so that patients can begin treatment if gout is suspected."

"Misdiagnosis or delayed diagnosis of gout may result in unnecessary surgery, hospitalization, delays in adequate treatment such as antibiotics for septic joints, and unnecessary prescribing of long-term treatment," the guideline cautions.

"Another new recommendation," Dr. Damle told Reuters Health, "is to start therapy without an aspiration of the joint in cases where the diagnosis is clear. In cases of uncertainty or possible infected joint, physicians should proceed first with a joint aspiration."

The guideline says there is not enough evidence at this time to support a single clinical algorithm for diagnosing gout, although several "promising" algorithms showed sensitivities and specificities greater than 80%. Current evidence is insufficient to support the use of dual-energy computed tomography (DECT) or ultrasonography to diagnose acute gout.

The ACP guidelines on diagnosis and treatment of gout are based on two systematic evidences review sponsored by the Agency for Healthcare Research and Quality's (AHRQ) and conducted by RAND's Southern California Evidence-based Practice Center.

SOURCES: https://bit.ly/2fonlMK, https://bit.ly/2e6Kmhe, https://bit.ly/2f2FcHH and https://bit.ly/2dWlyNV

Ann Intern Med 2016.

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